To provide an initial step toward the understanding of the functional relationship between the onc genes of transforming retroviruses and their cellular prototypes, structural comparisons at the nucleic acid and protein levels have been carried out. We have determined the complete nucleotide sequence of the chicken and human c-myc genes and compared them to the MC29 transforming gene (v-myc). Although a close relationship between the viral and cellular myc genes has been found, these genes are not isogenic. The myc-related genes of MC29, MH2, and OK10, and the myb-related genes of AMV and E26 are genetic hybrids with sequences derived from viral structural genes and parts of essential cellular proto-onc genes. The cellular genes contain additional 5' sequences. The substitution of viral genes for parts of the normal cellular genes may be the most significant difference between these genes, perhaps eliciting functional differences between their gene products. Using synthetic peptides as antigens, we have prepared myc-specific antisera. Immunoprecipitation of cellular extracts has allowed isolation of p110 (the MC29 transforming protein) from non-producer Q8 cells and p55 from chicken embryo fibroblasts. The overlapping tryptic peptide fingerprint pattern suggests that these two proteins have a common composition, offering the first conclusive evidence that defines p55 as the chicken cellular myc gene product. We have initiated studies of the cellular ets gene to determine whether this pattern of a truncated normal gene in the transforming retrovirus can be extended to other onc genes.